ObjectiveCongenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited.Design and methodsOne hundred ten patients with primary CH were recruited in this study. All exons and exon–intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees.ResultsOur results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands.ConclusionsMost cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.

epatitis B, which is caused by the hepatitis B virus (HBV), is a potential life-threatening liver infection and the most serious type of viral hepatitis. As the World Health Organization reported, 1 approximately 2 billion people have been infected with HBV worldwide, and more than 350 million people have chronic hepatitis B. In China, the most common viral hepatitis is type B. The final evolutionary stage of chronic hepatitis B is liver cirrhosis. Portal hypertension is a major cause of esophageal varices, which have been reported to occur in up to 90% of patients with cirrhosis. 2 -Ping Ye, MM, Hai-Tao Ran, MD, Juan Cheng, MM, Ye-Feng Zhu, MM, Da-Zhi Zhang, MD, Ping Zhang, MD, Yuan-Yi Zheng, MD Received November 14, 2011, Methods-Two hundred sixty-four participants, of whom 60 were healthy volunteers (classified as stage 0), 66 were patients with chronic hepatitis B who had undergone liver biopsy, and 138 were patients with hepatitis B-related cirrhosis, were enrolled in this study. Median liver and spleen stiffness values (meters per second) from 10 successful measurements per participant were obtained. Patients with cirrhosis were examined by upper endoscopy. XiaoResults-Significant linear correlations were found between liver (Spearman ρ = 0.87; P < .001) and spleen (Spearman ρ = 0.76; P < .001) stiffness and the fibrosis stage.Liver and spleen stiffness values increased as fibrosis progressed; however, overlaps in liver stiffness were detected in stages 0 and 1 and 1 and 2, and overlaps in spleen stiffness were observed in stages 0 and 1, 1 and 2, and 2 and 3. Liver stiffness cutoff values were 1.69 m/s for predicting stage 3 or greater (area under the receiver operating characteristic curve [AUROC] = 0.99) and 1.88 m/s for stage 4 (AUROC = 0.97). The spleen stiffness cutoff value was 2.72 m/s for stage 4 (AUROC = 0.96). Liver stiffness was not correlated with the varix grade, whereas a significant linear correlation (Spearman ρ = 0.65; P < .001) between spleen stiffness and the varix grade was found. The optimal spleen stiffness cutoff value for predicting varices was 3.16 m/s (AUROC = 0.83).Conclusions-Liver and spleen stiffness values measured by ARFI elastography are reliable predictors of liver fibrosis. Spleen stiffness measured by ARFI can be used as a noninvasive method for determining the presence and severity of esophageal varices; however, evidence to support a similar role for liver stiffness is lacking.

No abstract

No abstract

No abstract

Adipokines such as leptin play important roles in the regulation of energy metabolism, particularly in the control of appetite. Here, we describe a hormone, mimecan, which is abundantly expressed in adipose tissue. Mimecan was observed to inhibit food intake and reduce body weight in mice. Intraperitoneal injection of a mimecan-maltose binding protein (-MBP) complex inhibited food intake in C57BL/6J mice, which was attenuated by pretreatment with polyclonal antibody against mimecan. Notably, mimecan-MBP also induced anorexia in Ay/a and db/db mice. Furthermore, the expression of interleukin (IL)-1β and IL-6 was up-regulated in the hypothalamus by mimecan-MBP, as well as in N9 microglia cells by recombinant mouse mimecan. Taken together, the results suggest that mimecan is a satiety hormone in adipose tissue, and that mimecan inhibits food intake independently of leptin signaling by inducing IL-1β and IL-6 expression in the hypothalamus.

Background and purpose: Targeted therapy and immunotherapy have led to dramatic change in the treatment of lung cancer, however, the overall 5-year survival rate of lung cancer patients is still suboptimal. It is important to exploit new potential of molecularly targeted therapies. High-frequency somatic mutations in KEAP1/NRF2 (27.9%) have been identified in lung squamous cell carcinoma. In this research, we explored the role of KEAP1 somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target lung cancer carrying KEAP1/NRF2 mutations. Methods: Lung cancer cell lines A549 and H460 with loss-of-function mutations in KEAP1 stably transfected with wild-type (WT) KEAP1 or somatic mutations in KEAP1 were used to investigate the functions of somatic mutations in KEAP1. Flow cytometry, plate clone formation experiments, and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines. Results: The expression of NRF2 and its target genes increased, and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with KEAP1 mutants compared to control cells with a loss-of-function KEAP1 mutation and stably transfected with WT KEAP1 in both in vitro and in vivo studies. The proliferation of A549 cell line trasfected with the R320Q KEAP1 mutant was inhibited more apparent than that of the A549 cell line trasfected with WT KEAP1 after treatment with NRF2 inhibitor ML385. Conclusion: Somatic mutations of KEAP1 identified from patients with LSCC likely promote tumorigenesis mediated by activation of the KEAP1/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with KEAP1 mutation.

No abstract